As CRISPR emerges, re­searchers spot­light pos­i­tive ef­fects in pre­na­tal gene edit­ing treat­ment for mice

In a break­through for the buzzing world of CRISPR re­search, a team of sci­en­tists has demon­strat­ed a use of the gene edit­ing tool to treat a ge­net­ic dis­ease in mice be­fore they are born.

The proof-of-con­cept study brings them one step clos­er — though still miles away — to the ul­ti­mate goal of treat­ing se­vere hu­man dis­eases di­ag­nosed ear­ly in preg­nan­cy, ac­cord­ing to the re­searchers from Chil­dren’s Hos­pi­tal of Philadel­phia and the Perel­man School of Med­i­cine at the Uni­ver­si­ty of Penn­syl­va­nia.

William Per­an­teau

“A sig­nif­i­cant amount of work needs to be done be­fore pre­na­tal gene edit­ing can be trans­lat­ed to the clin­ic,” said study co-leader William Per­an­teau, a pe­di­atric and fe­tal sur­geon in CHOP’s Cen­ter for Fe­tal Di­ag­no­sis and Treat­ment. “Nonethe­less, we are ex­cit­ed about the po­ten­tial of this ap­proach to treat ge­net­ic dis­eases of the liv­er and oth­er or­gans for which few ther­a­peu­tic op­tions ex­ist.”

For their study, pub­lished in Na­ture Med­i­cine, the team com­bined two dif­fer­ent tech­niques: Us­ing the well-known CRISPR-Cas9 com­pound as a guide, they fused an en­zyme to it that chem­i­cal­ly mod­i­fies the ge­net­ic code once the com­pound ar­rived at the spec­i­fied ge­net­ic lo­ca­tion. Dubbed base ed­i­tor 3, this method is de­scribed as po­ten­tial­ly safer than the cut-and-paste mod­el of reg­u­lar CRISPR-Cas9, which re­searchers have warned could cause off-tar­get ef­fects.

But be­fore they test­ed the tool on a group of mice en­gi­neered to de­vel­op the lethal liv­er dis­ease hered­i­tary ty­rosine­mia type 1 (HT1), the in­ves­ti­ga­tors first tried it out with the PC­SK9 gene — a cho­les­terol reg­u­la­tor now tar­get­ed by a new class of car­dio drugs — and showed that the fe­tus­es re­ceiv­ing this treat­ment were born with sig­nif­i­cant­ly low­er cho­les­terol lev­els.

Sim­i­lar­ly, the in­tend­ed ef­fect was ob­served in new­born mice which had a re­lat­ed gene — not the dis­ease-caus­ing one — dis­abled in utero: They “car­ried sta­ble amounts of edit­ed liv­er cells for up to three months af­ter the pre­na­tal treat­ment, with no ev­i­dence of un­want­ed, off-tar­get edit­ing at oth­er DNA sites” with “im­proved liv­er func­tion and pre­served sur­vival.”

In fact, they did even bet­ter than mice born with HT1 that are sub­se­quent­ly treat­ment with ni­tisi­none and di­et, the cur­rent stan­dard of care for in­fants with HT1.

The in­ves­ti­ga­tors re­main cau­tious­ly op­ti­mistic about their ear­ly work, al­ready test­ing al­ter­na­tive de­liv­ery sys­tems to the ade­n­ovirus vec­tors used in this ex­per­i­ment, as it’s been sug­gest­ed that ade­n­ovirus vec­tors, a main­stay in gene ther­a­py ex­per­i­ments, may cause ad­verse re­spons­es from the host’s im­mune sys­tem. Oth­er di­rec­tions of re­search in­clude di­rect­ly edit­ing dis­ease-caus­ing genes and ex­plor­ing the tech’s ap­pli­ca­tion in oth­er or­gans.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Sanofi/Re­gen­eron mus­cle ahead of a ri­val No­var­tis/Roche team, win first ap­proval in key rhi­nos­i­nusi­tis field

Re­gen­eron and their part­ners at Sanofi have beat the No­var­tis/Roche team to the punch on an­oth­er key in­di­ca­tion for their block­buster an­ti-in­flam­ma­to­ry drug Dupix­ent. The drug team scored an ac­cel­er­at­ed FDA ap­proval for chron­ic rhi­nos­i­nusi­tis with nasal polyps, mak­ing this the first such NDA for the field.

An­a­lysts have been watch­ing this race for awhile now, as Sanofi/Re­gen­eron won a snap pri­or­i­ty re­view for what is now their third dis­ease in­di­ca­tion for this treat­ment. And they’re not near­ly done, build­ing up hopes for a ma­jor fran­chise.

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

Ab­b­Vie's $63B buy­out spot­lights the re­turn of ma­jor M&A deals — de­spite the back­lash

Big time M&A is back. But for how long?

Over the past 18 months we’ve now seen three major buyouts announced: Takeda/Shire; Bristol-Myers/Celgene and now AbbVie/Allergan. And with this latest deal it’s increasingly clear that the sharp fall from grace suffered by high-profile players which have seen their share prices blasted has created an opening for the growth players in big pharma to up their game — in sharp contrast to the popular bolt-on deals that have been driving the growth strategy at Novartis, Merck, Roche and others.

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Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Top an­a­lyst finds a sil­ver lin­ing in Ab­b­Vie’s $63B Al­ler­gan buy­out — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took a 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

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While Ako­rn works to re­vive its for­tunes, the FDA hits it with an­oth­er warn­ing let­ter

Ako­rn just can’t dig it­self out of its hole.

The spe­cial­ty gener­ic drug­mak­er has re­ceived yet an­oth­er warn­ing let­ter from the FDA this year. With­out dis­clos­ing any specifics, the Lake For­est, Illi­nois-based drug­mak­er on Wednes­day said the US reg­u­la­tor had is­sued the let­ter, cit­ing an in­spec­tion of its Som­er­set, New Jer­sey man­u­fac­tur­ing fa­cil­i­ty in Ju­ly and Au­gust of 2018. The com­pa­ny’s shares $AKRX dipped about 1.7% to $4.65 be­fore the bell.